Get Well Soon

In medical school we were taught that Type II DM is a chronic progressive disease - once diagnosed, it could potentially be managed, controlled, but never cured.

The primary thrust of diabetic cares has been to try and control blood sugar with a goal of decreasing the risk of macrovascular (heart attack and stroke) and microvascular (kidney failure and blindness).

Conventional wisdom has been that 90% of diabetics require medication treatments that need to intensified over time to effectively prevent complication and that "delays in intensification of are common and may be due to unrealistic patient expectations." (1)

Evidence is accumulating that conventional wisdom has been wrong.

The Massive Toll of Diabetes

Diabetes rates globally are rising, driven by the obesity epidemic. ​In Canada, 9% of the population is diabetic - this has grown from 3.3% in 1998 and is expected to grow to 12% in 2025.

Perhaps even more alarming, an additional 22% of the population are pre-diabetic, 90% of whom do not realize it. Over 70% of pre-diabetics will go on to develop diabetes.

Diabetes reduces lifespan by 5-15 years and accounts for over 10% of deaths in Canadian adults.

People with diabetes are:

over three 3 times more likely to be hospitalized with cardiovascular disease

12 times more likely to be hospitalized with end-stage renal disease and

over 20 times more likely to be hospitalized for a non-traumatic lower limb amputation compared to the general population.

Diabetics have a 25% greater chance of developing cancer. Diabetes is moderately associated with cancers of the:

Diabetes and depression create a self-enforcing viscous cycle: 30% of diabetics have clinically relevant depressive symptoms, people with depression have a 60% increased risk of developing type 2 diabetes.

Adding to this massive clinical toll, the cost of diabetic care is staggering - in Canada we currently spend $15B on treatment and management of complications. With the rates of diabetes climbing the cost trend has been called an economic tsunami, with an expected doubling by 2025.

Looked at from both the clinical and financial perspective, it is clear that diabetes is the biggest healthcare challenge of our generation.

Stepping back, we can see that our traditional approach:

eat less

avoid fat

exercise more

prescribe early

intensify medications to maintain glycemic control

prescribe other medications to control for other risk factors

hypertension

high cholesterol

... is not working, for the simple reason: our current approach does not address the cause of diabetes.

The chronic and progressive nature of diabetes may have more to do with our management than of the disease itself.

In part II and III of this blog series, I will look at the powerful new evidence that Type II Diabetes can be reversed through a comprehensive lifestyle approach.

At Wellness Garage, we believe that the answer to optimal health and vital longevity lies in our lifestyle behaviors. We use comprehensive, evidence-based, precision health assessments to gain deep understanding of an individuals current health and behaviors. We then use this information to come up with a behavioral plan to address underlying illness and risk, while optimizing health.

In the coming months, Wellness Garage will be launching a comprehensive diabetes program aimed at disease reversal and remission based on evidence from powerful new studies. Part II and Part III of this blog series will explore this evidence and detail the Wellness Garage approach.

As I have written elsewhere on this blog, cardio-respiratory fitness (V02Max) and muscle strength are both independent and powerful predictors of longevity.

Ruiz and colleagues carried out the most comprehensive study examining the influence of muscle strength and cardiorespiratory fitness on healthy aging. They found that for those over 60, both all-cause and cancer mortality is twice as likely in individuals with low compared to high skeletal muscle strength, and irrespective of strength, low cardio-respiratory fitness is associated with twice the incidence of all cause mortality.

Aging is characterized by a decline in the capacity of the body’s major organs, in particular the loss of muscle (sarcopenia) and loss of bone (osteopenia) have severe consequences on the quality of life as we age. From a metabolic perspective, a healthy muscle mass with frequent exercise provides a sink for glucose, making it easier to maintain blood sugars and avoid insulin resistance. The decline of healthy, functional, skeletal muscle, correspondingly is one of the major factors leading to insulin resistance, with higher levels of insulin causing inappropriate fat deposition throughout the body further compromising organ function. Quite separate from the metabolic effects of diminished muscle mass, the loss of functional endurance, strength and range of motion effects locomotory function, compromises balance, increases risk of falls and fractures and leads to diminished health span.

Given the clear benefits of muscle strength on healthy aging one key question is what should you do to preserve muscle mass, strength and function across lifespan?

There is clear evidence that the trajectory of sarcopenia and muscle loss is highly dependant on activity - in other words exercise dramatically diminishes the loss of muscle associated with age.

Repeated resistance exercise results in increased muscle mass by stimulating protein synthesis within the muscle. With aging there is evidence that there is some anabolic resistance to the effect of exercise but that this can be overcome if a sufficient stimulus is maintained.

Protein is the essential macronutrient in the diet for the maintenance of muscle strength, mass and function. The current RDA for protein intake to meet whole-body metabolic demands has been stet at 0.8g/kg/day - but this guideline does not differentiate between young and old or between individuals looking to gain or maintain muscle mass. As with many things nutrition related, these one-size fits all metrics don’t make much sense. A better way to think about protein intake, is that they should be optimized to levels that promote maintenance of muscle mass throughout the lifespan.

An interesting recent review looked much more closely at this question of how much protein is optimal if you are trying to gain muscle. This meta analysis found that weight lifting regardless of protein supplementation led to strength gains, but for those who increased their protein strength was increased by about 10% and muscle mass by about 25%. When looking for the optimal amount of protein, the sweet spot seems to be around 1.6 mg/kg/day - or roughly twice the RDA. Above this level there was no additional advantage. Interestingly this review did not find any advantage to the type or timing of the protein intake. This may be because the underlying studies were very small, as there is basic science support for the notion that the muscle’s anabolic response to amino acids is maximal in the post workout period and that branded chain amino acids (BCAA’s), in particular leucine are the most potent stimulators of anabolism through the mTOR pathway.

Here's the bottom line:

maintaining muscle mass and function is very important for vital longevity

regular resistance work can decrease the age related loss of muscle and bone (the negative corollary is that sedentary lifestyle will accelerate the natural losses)

pushing protein intake to 1.6 mg/kg/day - for a 70kg man this corresponds to 448 calories coming from protein - which is still only about 20% of total calories (there really is no need to push protein beyond this level)

While I won’t get in too much detail here, I would like to point out that when it comes to macronutrient levels there is no simple formula that fits everyone - in fact this is something that needs to be adjusted to each person’s unique genetics, environment and behaviours.

For proteins, we have just seen that the optimal level of protein needs to be adjusted to the level of anabolism - more muscle mass increase requires more protein, maintenance less, and under no circumstances do we want the dietary intake of protein to trigger catabolism or muscle breakdown. So we need to define protein intake by the person’s goals - maintenance or anabolism - and adjust accordingly. Dietary proteins that are not used for the body’s protein repair, maintenance and increase of muscle mass, are generally excreted and not used for energy provision.

In many ways, our protein rule is to find the minimum level of protein that meets our goals - maintenance or anabolism.

For carbs the task is reversed, we should titrate the maximal amount of carbs that we can tolerate while maintaining low and flat blood sugars without any sign of insulin resistance. For people that are already showing insulin resistance, this level will be very low - hence the low carb approach for metabolic disease. For others, (healthy cross-fitters for example), burning lots of calories in metabolically healthy muscles the amount will be higher.

And that brings us to fat, the calories that we do not get from carbs to meet our daily requirements must come from fat. Our energy requirements must be met by our intake of fats and carbs. So it you have insulin resistance and are carb intolerant, your fat intake must increase.

For today, I will leave it here, but add one last comment, the most important thing to remember about anything related to nutrition is that the source of any of your calories should be coming from nutrient dense whole foods that are not processed or refined.

Humans need to eat. Cells throughout the body are predominantly fueled by glucose delivered through the blood.

In evolutionary times food was not predictable, most often scarce, sometimes abundant. To maintain a consistent energy supply of blood glucose, evolution created a complex signaling system to control the process, delivering glucose when it is needed and efficiently storing it, when calories are abundant, ready to be mobilized in times of scarcity. Two hormones are central to this signaling process: insulin and glucagon. When blood sugar drops, pancreatic alpha cells release glucagon which then triggers the release of glucose from the liver. Correspondingly, when blood sugars rise, pancreatic beta cells release insulin which promotes glucose uptake in the liver and muscle, storing it as glycogen initially and then when glycogen stores are maximized, insulin prompts the conversion of carbohydrates and proteins to fat, our most efficient way to store calories for the future. Both insulin and glucagon are small proteins recognized by specific receptors on individual cells.

This process, developed over 600M years of evolution, now is under challenge in humans. The conditions for which we are optimized: calorie scarcity with intermittent abundance, no longer exist. Instead we live in a world of continuous excess calories, with processed foods that rapidly spike blood sugars and trigger massive insulin release, and correspondingly massive insulin directed storage of excess calories as fat in adipose tissue.

For many this process has become a one-way street, the flexibility to shift metabolically from glucose to fat as fuel that was once the key to our survival has, for many people, been lost. They are dependent on maintaining blood sugars through the constant consumption of carbohydrates. - if you find yourself craving sweats, getting tired after eating and feeling generally fatigued - this could be happening to you.

As a result of excess calories, sedentary lifestyles and this loss of metabolic flexibility, global levels of obesity are soaring: 2 Billion people are overweight - 650M are obese. In Canada close to 50% of the population is overweight!. With obesity has come a corresponding epidemic of obesity related diseases:

Non-alcoholic fatty liver disease (NAFLD) - 75% of people who are obese are at risk for NAFLD

The process underlying this epidemic of epidemics is insulin resistance.

The cellular mechanisms by which insulin resistance manifests are complex and beyond the scope of this blog, but at a high level, dysfunctions in three areas appear to alone, or in combination affect the ability of insulin to efficiently activate the insulin receptor and trigger the cascade of reactions that allows insulin to do it's job:

ectopic lipid accumulation - lipids build up within the cells and in turn adversely affecting the insulin signaling pathways

unfolded protein response and endoplasmic reticulum stress - the endoplasmic reticulum is the organelle where complex proteins - including cell membrane receptors - are folded to gain their functional state. A build up of mis-shaped proteins triggers the unfolded protein response that in turn leads to intracellular lipid accumulation, inflammation and in pancreatic beta cells affects insulin biosynthesis and can eventually lead to the cellular death of the beta cells - a key step in the progression of Type II Diabetes.

inflammatory response - activation of the inflammatory systems - starting with activated macrophages in adipose cells over-run with fat, results in a cascaded release of multiple inflammation signals - molecules called cytokines. These inflammatory signals themselves disrupt the normal action of insulin and lead to disruption of normal metabolic processes.

The process by which insulin resistance progresses to pre-diabetes and diabetes is understandable and predictable - it is also very preventable.

As insulin resistance sets in, muscle, fat, and liver cells do not respond properly to insulin and thus cannot easily absorb glucose from the bloodstream. As a result, the body needs higher levels of insulin to help glucose enter cells.

The beta cells in the pancreas try to keep up with this increased demand for insulin by producing more. As long as the beta cells are able to produce enough insulin to overcome the insulin resistance, blood glucose levels stay in the normal range.

Over time, the processes that led to insulin resistance in the first place cause pancreatic beta cells to become less efficient and eventually triggers beta cell death. As this begins to happen, blood sugars fall out of the normal range and people begin to be diagnosed with pre-diabetes or diabetes on the basis of abnormal blood sugars.

The time that it takes to progress from insulin resistance to pre-diabetes is generally in the order of 10-15 years - during this whole time a person will have normal blood sugars and may feel reassured that they do not have diabetes - YET - they are manifesting the underlying process of insulin resistance that will lead to diabetes and it's complications.

So the big question that you should be asking is - how do I know whether I have insulin resistance?Direct testing of insulin response is not broadly available, so we are most often left looking for other signs of insulin resistance.For the most part, we can work with this:

advanced metabolomic testing from Molecular You will also provide clues that insulin resistance is present (elevations in branched-chain amino acids for example)

the accumulation of visceral fat (measured by DXA or by tape-measure) is also highly correlated with insulin resistance.

hsCRP will give us a good measure of underlying inflammation which generally accompanies insulin resistance to some extent.

and of course we can check blood sugars and HbA1c (the 120 average of blood sugars) but these will be normal until insulin resistance becomes pre-diabetes.

My blood sugars are normal, but I think I have insulin resistance, what do I doThe good news is the process that leads to diabetes is reversible through lifestyle changes:

Food first - the absolute first step is to correct the patterns of eating that have led to insulin resistance. Eliminating refined carbohydrates, eating a variety of whole foods, shifting to a mostly plant-based diet are all solid strategies. More aggressive therapeutic nutrition strategies like a ketogenic diet have been shown to be very successful but definitely warrant medical direction and monitoring (especially if you are diabetic on medications).

Activity - nothing crazy here - but building up your aerobic base will help restore a degree of metabolic flexibility as your body learns to burn fat while you exercise. Weight lifting dramatically improves metabolic health by improving mitochondrial function.

Sleep - undiagnosed sleep issues like sleep apnea can lead to obesity and insulin resistance. If you snore or your spouse notices that you stop breathing in your sleep, you should get yourself screened for sleep apnea. It is relatively straightforward and it is free. Wellness Garage works with Clinical Sleep Solutions.

One of the major reasons we started Wellness Garage was to help people intervene early in preventable disease processes like insulin resistance rather than wait until blood sugars become abnormal (after 10-15 years!) and prescribe medications.